Entecavir: A new treatment option for chronic hepatitis B
ABSTRACT Because of the slow kinetics of viral clearance and the spontaneous genetic variability of hepatitis B virus (HBV), antiviral therapy of chronic hepatitis B remains a clinical challenge. Despite the recent development of lamivudine, adefovir dipivoxil and pegylated interferon alpha for the treatment of chronic HBV infection, there is still a major need for new antiviral compounds. Entecavir, a guanosine analog, has been recently approved in US for the therapy of chronic hepatitis B and its registration is expected soon in Europe. Extensive studies have been performed to characterize its antiviral activity in enzymatic and tissue culture models, as well as in animal models of HBV infection. In clinical trails, entecavir administration was associated with a significantly more potent viral suppression compared to lamivudine, and a significant advantage in terms of biochemical and histological improvement compared to lamivudine. Entecavir was tolerated as well as lamivudine in these phase III trials. No case of resistance was detected after two years of therapy in nucleoside naive patients. Treatment of patients with lamivudine failure requires a higher dosage of entecavir and induces a significant decline in viraemia levels. However, 10% of these patients developed entecavir resistance after two years of therapy. The availability of entecavir as a new treatment option is providing clinicians more choice to keep both viral replication and liver disease under control. This provides new hope for improved treatment concepts for chronic HBV infection.
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ABSTRACT: Development of hepatitis B virus (HBV)-resistant strains following nucleos(t)ide analog treatment is a major medical concern. This report describes a case of an adult patient with chronic HBV infection, sequentially treated with the nucleos(t)ide analogues, lamivudine, adefovir, and entecavir. During monotherapy with lamivudine, the patient developed lamivudine-resistant variants, which were undetectable during adefovir dipivoxil monotherapy. Twenty-two months after discontinuing lamivudine therapy, the resistant variants were again detected while the patient was receiving entecavir monotherapy. Genotypic analysis by sequencing the HBV polymerase was confirmed with the INNO-LiPA method. The results of this study suggest that entecavir treatment reselected residual lamivudine-resistant HBV variants, possibly because lamivudine-resistant HBV is less susceptible to entecavir than the wild-type virus. Despite the presence of these variants, the patient has had a complete virological response.Journal of Medical Virology 11/2007; 79(11):1671-3. DOI:10.1002/jmv.20982 · 2.22 Impact Factor
- Hepatology 12/2006; 44(6):1404-7. DOI:10.1002/hep.21451 · 11.19 Impact Factor
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ABSTRACT: More than 40 compounds have been formally licensed for clinical use as antiviral drugs, and half of these are used for the treatment of HIV infections. The others have been approved for the therapy of herpesvirus (HSV, VZV, CMV), hepadnavirus (HBV), hepacivirus (HCV) and myxovirus (influenza, RSV) infections. New compounds are in clinical development or under preclinical evaluation, and, again, half of these are targeting HIV infections. Yet, quite a number of important viral pathogens (i.e. HPV, HCV, hemorrhagic fever viruses) remain in need of effective and/or improved antiviral therapies.